Known in the art are various urokinase derivatives, for example, water-soluble urokinase derivatives suitable for therapeutic purposes comprising complexes of the enzyme of urokinase with heparin or dextran sulphate (cf. U.S. Pat. No. 4,106,992; 1978; Japanese Pat. No. 159387, 1977).
These urokinase derivatives are, however, unstable.
When penetrating into blood circulation, they cause destruction of electrostatic interactions with the formation of substantially a mixture of urokinase with the vehicle, which is accompanied by a rapid inactivation of the enzyme and discontinuation of the thrombolytic effect.
Also known in the art are urokinase derivatives comprising urokinase covalently bonded with dextran (cf. Japanese Pat. No. 54-113488, 1979).
These derivatives are water-soluble and feature an enhanced stability. However, such modification of the enzyme does not ensure its affinity for the thrombus material, wherefore an enhanced fibrinolytic activity of blood with the use of such derivatives still does not guarantee an effective process of thrombolysis.